Background: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy.
Methods: The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers.
Results: The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%.
Conclusions: This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients.
Keywords: blood test; epigenetics; immune checkpoint inhibitors; immuno-oncology; response to treatment.